title: Regulation of CuZnSOD and its redox signaling potential: implications for amyotrophic lateral sclerosis.
abstract: CONCLUSIONS
  Molecular oxygen is a Janus-faced electron acceptor for biological systems, serving as a reductant for respiration, or as the genesis for oxygen-derived free radicals that damage macromolecules. Superoxide is well known to perturb nonheme iron proteins, including Fe/S proteins such as aconitase and succinate dehydrogenase, as well as other enzymes containing labile iron such as the prolyl hydroxylase domain-containing family of enzymes; whereas hydrogen peroxide is more specific for two-electron reactions with thiols on glutathione, glutaredoxin, thioredoxin, and the peroxiredoxins.
  
  
  BACKGROUND
  Over the past two decades, familial cases of amyotrophic lateral sclerosis (ALS) have been shown to have an association with commonly altered superoxide dismutase 1 (SOD1) activity, expression, and protein structure. This has led to speculation that an altered redox balance may have a role in creating the ALS phenotype.
  
  
  RESULTS
  While SOD1 alterations in familial ALS are manifold, they generally create perturbations in the flux of electrons. The nexus of SOD1 between one- and two-electron signaling processes places it at a key signaling regulatory checkpoint for governing cellular responses to physiological and environmental cues.
  
  
  CONCLUSIONS
  The manner in which ALS-associated mutations adjust SOD1's role in controlling the flow of electrons between one- and two-electron signaling processes remains obscure. Here, we discuss the ways in which SOD1 mutations influence the form and function of copper zinc SOD, the consequences of these alterations on free radical biology, and how these alterations might influence cell signaling during the onset of ALS.
authors.affiliation: 1 Department of Radiation Oncology, Kaiser Permanente Los Angeles Medical Center , Los Angeles, California.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hitchler
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D006801:Humans; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism
chemical_list: C000606290:SOD1 protein, human; D013481:Superoxides; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1